Anti-Ro52 Seropositive Interstitial Lung Disease is Associated with a Higher Risk for Disease Progression and Mortality.

Abstract

Background: Identifying biomarkers is vital for interstitial lung disease (ILD) management and prognostication. While anti-Ro52 antibodies are frequently detected in autoimmune diseases, their significance in ILD remains unclear.

Research question: What is the prognostic significance of anti-Ro52 positivity in patients with ILD?

Study design and methods: This retrospective cohort study used an ILD registry of patients seen at an academic tertiary hospital's ILD clinic between 2015 and 2024. All patients diagnosed with ILD and tested for anti-Ro52 antibody status were divided into anti-Ro52 positive (Anti-Ro52+) and negative (Anti-Ro52-) groups. The primary outcome was ILD progression or all-cause death. ILD progression was defined as any of the following: hospitalization due to ILD; absolute decline in forced vital capacity percent of predicted value ≥10% from baseline; or lung transplantation. Kaplan-Meier method and Cox proportional hazards regression model were used for survival analysis.

Results: Of 1,026 patients tested for the anti-Ro52 antibody (median age: 70 years; 52% male), 154 (15%) were Anti-Ro52+. Underlying ILD subtypes were as follows: interstitial pneumonia with autoimmune features (IPAF) (n = 489, 48%), connective tissue disease-ILD (n = 132, 13%), idiopathic pulmonary fibrosis (n = 103, 10%), hypersensitivity pneumonitis (n = 61, 6%), and other idiopathic ILD (n = 241, 24%). The Anti-Ro52+ group was younger (median age 67 vs. 70 years), was more likely to have CTD (28% vs. 10%) and more frequently had a copositive myositis-specific antibody (29% vs. 16%). After a median follow-up of 25.6 months, anti-Ro52+ subjects had a higher risk of ILD progression or death (hazard ratio 2.10; 95% CI, 1.61-2.73; P<0.001) and had a higher risk of lung transplant or death (hazard ratio 1.61; 95% CI, 1.11-2.35; P=0.014) on multivariable analysis.

Interpretation: Anti-Ro52 seropositive ILD is associated with significantly worse progression-free and transplant-free survival and may inform disease prognostication and monitoring.